Case Presentation: A 42-year-old female presented to the emergency department with a 2-week history of jaundice, intermittent abdominal pain, hip pain, and fevers. Her past medical history was significant for ankylosing spondylitis. She was on chronic immunosuppression with prednisone, Plaquenil and Infliximab. Initial evaluation was remarkable for abnormal liver function and thrombocytopenia (Table 1). The patient was initially treated with broad-spectrum antibiotics for suspected acute cholangitis. Further imaging studies, including abdominal ultrasound, HIDA scan, and Magnetic Retrograde Cholangiopancreatography, were not definitive for an acute gallbladder pathology thus a liver biopsy was obtained and revealed numerous intracellular organisms that were morphologically compatible with Histoplasma capsulatum. Due to complicated hospital course with persistent fevers, seizures, acute kidney injury and altered mental status a hematologic evaluation was performed; this included ferritin, triglycerides (Table 1), and peripheral smear showing toxic granulocytes and band forms. Bone marrow biopsy revealed hemophagocytic cells and aspirate with a Gomori methenamine silver stain was positive for fungal yeast forms. Since the patient met diagnostic criteria for Haemophagocytic lymphohistiocytosis, dexamethasone was given for a total of 6 weeks and etoposide for 2 doses. The patient also received Amphotericin B for 14 days and was transitioned to oral Itraconazole. Significant clinical improvement was noted and ultimately discharged in stable condition.
Discussion: Discussion: Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. Secondary HLH is often triggered by autoimmune diseases, malignancies, or infections. The pathogenetic mechanisms behind HLH are not completely understood but involve cytotoxic lymphocyte dysfunction, leading to an exaggerated inflammatory response. The consequence of this is tissue damage and progressive multiple-organ failure. The spleen, liver, and lungs are most frequently affected, but HLH can involve virtually all tissues in the body. In the presented case, the initial presentation was suggestive of acute cholangitis but additional features and diagnostic studies were required to determine a final diagnosis. Histoplasmosis often has an asymptomatic course on immunocompetent hots but given the history of chronic immunosuppression, the patient was at risk of developing a severe infection. The complicated hospital course was consistent with superimposed HLH secondary to Disseminated Histoplasmosis.
Conclusions: Patients with HLH are often severely ill and might present with multiple confounding factors, which makes the diagnostic approach challenging. The case illustrates the importance of a high degree of suspicion and comprehensive evaluation necessary for the diagnosis of HLH. This diagnosis should never be considered complete without looking for triggering factors. Our case illustrates an unusual presentation of an infection with a superimposed rare condition representing a diagnostic challenge.
